title: Established thymic epithelial progenitor/stem cell-like cell lines differentiate into mature thymic epithelial cells and support T cell development.
abstract: Common thymic epithelial progenitor/stem cells (TEPCs) differentiate into cortical and medullary thymic epithelial cells (TECs), which are required for the development and selection of thymocytes. Mature TEC lines have been widely established. However, the establishment of TEPC lines is rarely reported. Here we describe the establishment of thymic epithelial stomal cell lines, named TSCs, from fetal thymus. TSCs express some of the markers present on tissue progenitor/stem cells such as Sca-1. Gene expression profiling verifies the thymic identity of TSCs. RANK stimulation of these cells induces expression of autoimmune regulator (Aire) and Aire-dependent tissue-restricted antigens (TRAs) in TSCs in vitro. TSCs could be differentiated into medullary thymic epithelial cell-like cells with exogenously expressed NF-κB subunits RelB and p52. Importantly, upon transplantation under the kidney capsules of nude mice, TSCs are able to differentiate into mature TEC-like cells that can support some limited development of T cells in vivo. These findings suggest that the TSC lines we established bear some characteristics of TEPC cells and are able to differentiate into functional TEC-like cells in vitro and in vivo. The cloned TEPC-like cell lines may provide useful tools to study the differentiation of mature TEC cells from precursors.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhan
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Su
authors.forename: Yarui
authors.initials: Y
authors.lastname: Du
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xu
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
authors.forename: Xiaoren
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D017931:DNA Primers; D014157:Transcription Factors; D000096927:AIRE Protein